• Korean Journal of Pharmacognosy
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• v.48 no.2
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• pp.155-159
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• 2017

Cudrania tricuspidata Bureau (Moraceae) is a traditional oriental medicine that has been widely used as anti-oxidant, anti-inflammatory and immunomodulatory in Korea. This study was performed that the 70% ethanol extract of the roots of C. tricuspidata (CTE) suppressed receptor activator of NF-${\kappa}B$ ligand (RANKL)-induced osteoclastogenesis, actin ring formation in RAW 264.7 cell lines. CTE significantly inhibited the JNK/mitogen-activated protein kinase (MAPK) signaling pathway without affecting ERK and p38 signaling in RANKL-stimulated RAW 264.7 cells. Also, CTE inhibited RANKL-induced expression of c-Fos, an upstream activator of NFATc1. Consequently, CTE suppresses osteoclast differentiation by inhibiting RANKL induced MAPK signaling pathways and disrupts the actin rings in mature osteoclasts. Thus, CTE can be used for the development of osteoporosis treatment drug with a natural material.

• YAKHAK HOEJI
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• v.48 no.3
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• pp.197-201
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• 2004

Phosphodiesterases (PDEs) are enzymes that degrade intracellular cAMP. In the present study, pentoxifylline, a PDE inhibitor, induced osteoclast formation in co-cultures of mouse bone marrow cells and calvarial osteoblasts. To address the involvement of the osteoclast differentiation factor TNF-related activation-induced cytokine (TRANCE, identical to RANKL, ODF, and OPGL), mouse bone marrow cells and calvarial osteoblasts were co-cultured with pentoxifylline in the presence of OPG, a decoy receptor for TRANCE. The osteoclastogenic effect of pentoxifylline was completely blocked by addition of OPG, suggesting that TRANCE is involved in the osteoclast formation induced by pentoxifylline, Northern blot analysis revealed that pentoxifylline significantly induced TRANCE mRNA expression in calvarial osteoblasts. These results suggests that pentoxifylline regulates TRANCE expression in osteoblasts, which in turn controls osteoclast formation.

• The korean journal of orthodontics
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• v.27 no.2
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• pp.335-347
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• 1997

Vitamin D is known to exert its action by activating DNA and RBA within target cells to produce proteins and enzymes that can be used in bone resorption process. Particularly, the active form of vitmain D, 1,25-dihydroxycholecalciferol $[1,25-(OH)_2D_3]$, is considered to be one of the most potent stimulators of osteoclatic acitivity in vitro. The purpose of this study was to evaluate the effect of 1,25-Dihydroxyvitamin $D_3$ on the avtivity of periodotal ligament cells and, the experimental tooth movement. Human periodontal ligament cells were collected from the first premolar tooth extracted for the orthodontic treatment, and were incubated in the environment of $37^{\circ}C$, 5% $CO_2$ and 95% humidity. Microtitration(MIT) assay was done at 10, 25, 50 and 100ng/ml of 1,25-Dihydroxyvitamin $D_3$. 21 Sprague-Daft rats were divided into a control gmup(3), and experimental groups(18) where 100g of force from helical spring was applied across the maxillary incisors 1,25-Dihydroxyvitamin $D_3$ was injected into periodontal ligament at the mesial or distal surface of maxillary incisors so that we can compare the control side and the experimental side. Expreimental groups were sac rifled at 12, 24, 36, 48, 72hours and 7 days after force application, respectively. And the obtained tissues were evaluated histologically. The observed results were as follows. 1. The activity of periodontal ligament cells in l0ng/ml or 25ng/ml of 1,25-Dihydroxyvitamin $D_3$ 1,25-Dihydroxyvitamin $D_3$ was not significantly different to the control at the cultivation of 1, 2 and 3 days. 2. The activity of periodontal ligament cells was significantly increased at 3 days in 50 ng/ml of 1,25-Dihydroxyvitamin $D_3$ and 2, 3 days in 100g/ml of 1,25-Dihydroxyvitamin $D_3$. 3. Up to 7 days after force application, there was no difference in osteoblastic activity, tearing of periodontal ligament and proliferation of capillary at tension side between 1,25-Dihydroxyvitamin $D_3$ injection side and the control side. 4. The osteoclastic activity and the resorption of alveolar bone was greater in 1,25-Dihydroxyvitamin $D_3$ injection side than the control side at 36 hours after force application.

• The Journal of Korean Obstetrics and Gynecology
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• v.26 no.2
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• pp.1-16
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• 2013

Objectives: This study was performed to evaluate the effect of Dokhwalgisaengtang-gami water extract(DGG) on osteoporosis. Methods: The osteoclastogenesis and gene expression were determined in RANKL-stimulated RAW 264.7 cell. And osteoblastogenesis was also determined in rat calvarial cell. Results: The results were summarized as followes. 1. DGG decreased the number of TRAP positive cell in RANKL-stimulated RAW 264.7 cell. 2. DGG inhibited TRAP activity in RANKL-stimulated RAW 264.7 cell. 3. DGG decreased the expression of NAFTc1, MITF in RANKL-stimulated RAW 264.7 cell. 4. DGG increased the expression of iNOS, COX-2, IL-6 in RANKL-stimulated RAW 264.7 cell. 5. DGG decreased the expression of cathepsin K, MMP-9, TRAP in RANKL-stimulated RAW 264.7 cell. 6. DGG increased cell proliferation of rat calvarial cell. 7. DGG increased ALP activity in rat calvarial cell 8. DGG increased bone matrix protein, collagen synthesis and nodule formation in rat calvarial cell. Conclusions: It is concluded that DGG might decrease the bone resorption resulted from decrease of osteoclast differentiation and it's related gene expression. And DGG might increase the bone formation resulted from increase of osteoblast function.

• The Journal of Korean Obstetrics and Gynecology
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• v.29 no.2
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• pp.66-82
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• 2016

Objectives : This study was conducted to evaluate the effect of Kanghwalsokdan-tang Gamibang water extract (KSG) on osteoporosis. Methods : RANKL-stimulated RAW 264.7 was used to evaluate inhibitory effect of KSG osteoclast differentiation and gene expression. We counted TRAP (+) multinucleated cells and measured TRAP activity and mRNA expressions of osteoclastogenesis-related genes (NFATc1, MITF, JNK1, cathepsin K, MMP-9) to figure out the effect of KSG on osteoclast. Osteoblastogenesis was also determined in rat calvarial cell. Alkaline phosphatase (ALP) activity, bone matrix protein and collagen synthesis were measured by using murine calvarial cell. Results : KSG inhibited the differentiation of osteoclast precursor cell and expression of genes related osteoclastogenesis like NAFTc1, MITF, c-fos, JNK1, Cathepsin K, MMP-9 and TRAP. KSG increased cell division and function of osteoblast separated from the skull of a rat and ALP synthesis, biosynthesis of bone matrix protein and collagen. Conclusions : Reviewing these results, KSG has efficacy on osteoclast inhibition and osteoblast activation. After further study, KSG will be able to apply for osteoporosis treatment and prevention.

• Journal of Physiology & Pathology in Korean Medicine
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• v.33 no.3
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• pp.169-174
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• 2019

The purpose of this study was to evaluate the inhibitory effects of Juglans regia complex extract(JCE) consisted of Juglans regia, Eucommia ulmoides, Eleutherococcus senticosus and Zingiber officinale on osteoclast differentiation. Cell toxicity test by using CCK-8, TRAP activity and TRAP positive multi-nucleated cell counting were performed to evaluate inhibitory effect on differentiation of osteoclast from bone marrow derived macrophages(BMMs) induced by receptor activator of nuclear $factor-{\kappa}B$ ligand(RANKL). As a result, JCE inhibited RANKL-induced osteoclast differentiation in BMMs dose-dependently without cytotoxicity. These results suggest that JCE may have a potential role for treating bone lytic diseases such as osteoporosis.

• Journal of Life Science
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• v.29 no.12
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• pp.1337-1344
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• 2019

Osteoporosis is characterized by a reduction in bone mass and typically manifests as an increase in fractures. Because this disease is common in elderly populations and lifespans are rapidly increasing, the incidence of osteoporosis has also grown. Most drugs currently used for osteoporosis treatment target osteoclasts in the bone tissue to prevent absorption. However, these medications also cause certain side effects and, furthermore, cannot increase bone mass. Thus, in order to control osteoporosis, regenerative medicine that utilizes adult stem cells and osteoblasts has been extensively studied. Statins, also known as 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, are cholesterol-lowering drugs that have been widely prescribed for cardiovascular diseases. Interestingly, recent studies have reported the beneficial effects of various statins on bone formation via the activation of osteoblasts. Thus, the current study investigated the effects of seven statin-family drugs on osteoblast activity during osteogenic differentiation using adult stem cells from human periosteal tissue. Specifically, statin effects on alkaline phosphatase activity, an early marker of bone cell differentiation, and on calcium deposit, a late marker of bone cell differentiation, were assessed. The results demonstrate that some statins (for example, pitavastatin and pravastatin) have a weak but positive effect on bone formation, and the findings therefore suggest that statin treatments can be a novel modulator for osteogenic differentiation and regenerative medicine using periosteal stem cells.

• Journal of the korean academy of Pediatric Dentistry
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• v.27 no.2
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• pp.309-317
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• 2000

Bisphosphonates inhibit bone resorption in vivo and in vitro. Currently proposed mechanism of action of bisphosphonates involves both direct effect on osteoclasts and indirect effect through the mediation of osteoblasts. Recent understanding of molecular mechanism of osteoclastogenesis indicates that osteoclast differentiation is quite tightly regulated by signaling molecules from differentiating osteoblasts. Therefore this investigation was designed to elucidate the effect of bisphosphonate on osteoblast differentation. For this purpose, in vitro effects of etidronate and alendronate on the expression of Cbfa1 a master control gene of osteoblast differentiation, several bone marker genes, and formation of calcified nodules were evaluated. To evaluate the effect of bisphosphonate on calcified nodule formation, osteoblasts isolated from rat calvaria were cultured in a-MEM containing $10^{-4},\;10^{-5},\;10^{-6}M$ of etidronate or $10^{-6},\;10^{-7},\;10^{-8}M$ of alendronate for 15 days, and then stained by alizarin red to determine mineralization. To evaluate the effect of bisphosphonate on osteoblast differentiation, osteoblast cells were cultured in a-MEM containing $10^{-4},\;10^{-5},\;10^{-6}M$ of etidronate or $10^{-6}$ M of alendronate for 8 days. And then total RNA was extracted and northern blot analysis was done to examine the expression of Cbfa1, type I collagen, alkaline phosphatase, osteopontin and osteocalcin. The results were as follows: 1. Etidronate suppressed the calcification of bone nodule in dose dependent manner, while alendronate didn't. 2. The expression of Cbfa1 was decreased dose dependently by etidronate, but increased by alendronate. 3. Etidronate suppressed the expression of type I collagen, osteopontin and osteocalcin in dose dependent manner however alendronate promote the expression of osteoblast marker gene. 4. The expression of alkaline phosphatase was not affected either etidronate nor alendronate. These results suggest that etidronate suppressed the expression of Cbfa1 in dose dependent manner, and consequently the expression of osteoblast marker genes, such as type I collagen, osteopontin and osteocalcin were also suppressed in similar manner. And finally this decreased expression of osteoblastic marker gene prevent calcined bone nodule formation.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.7
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• pp.929-936
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• 2005

The purpose of this study was to examine the ability of alkaline phosphatase (ALP) synthesis of MC3T3-E1 cells when above edible sources, Solidago virga-aurea var. gigantea Miq. root (SVR) extracts, were supplimented. MC3T3-E1 cells were cultured with $\alpha-MEM$(vehicle control), dexamethasone and genestein (positive control), and SVR extracts for 27 days. The effects of SVR MeOH extracts and its fractions on cell proliferation were measured by MTT assay. At 10, 100${\mu}g/mL$ of SVR methanol extract treated, that were elevated of cell proliferation to 140 and $120\%$ via vehicle control, respectively. And then ALP synthesis was measured by spectrophotometer for enzyme activity and by naphthol AS-BI staining for morphometry at 3, 9, 18, and 27th day. As the results, every extracts and fractions were promoted ALP activity by time course at 1, 10, 100${\mu}g/mL$, except n-hexane and chloroform fractions. Remarkably, the MeOH extracts were increased ALP activity more than 4.4 times compared with vehicle control, 2.2 times via positive control at 27th day (p<0.05). The SVR MeOH extracts treated cells, especially at a concentration of 10${\mu}g/mL$, showed remarkably higher than vehicle-treated control cells of mineralization which were checked by Alizarin red staining. These results indicate that SVR methanol extract have an induction ability of proliferation and differentiation on osteoblast.

• The Journal of the Korean bone and joint tumor society
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• v.10 no.1
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• pp.45-49
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• 2004

Chondroblastoma is a benign chondroid-forming tumor usually originating in the epiphysis. The base of metatarsal bone contains neither an epiphysis nor a secondary ossification center and so is the rare site of chondroblastoma. Here, we present a case of chondroblastoma of the base of fifth metatarsal bone in 34-year-old man. Histologically, the osteoclast-like giant cells were abundant enough to simulate a giant cell tumor. And the chondroid intercellular matrix was intermixed but scanty. However, the background mononuclear cells showed irregular and indented nuclei with longitudinal clefts and positive immunoreactivity for S-100 protein, as the evidence of chondroblasts.